Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock
Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock
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DOI：
10.1097/00003246-200101000-00026
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发表时间：
2001-01-01
影响因子：
8.8
通讯作者：
Rackow, EC
中科院分区：
文献类型：
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作者：
Sfeir, T;Saha, DC;Rackow, EC
目的：本研究的目的是检查内毒素刺激的脓毒症单核细胞中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10的释放模式，并确定IL-10和转化生长因子（TGF）-β在单核细胞中的作用脓毒症休克期间的低反应性。设计：将从10名健康对照和10名感染性休克患者中分离的单核细胞与内毒素一起孵育，并评估细胞因子释放。接下来，将正常单核细胞与正常或脓毒症血清一起孵育，并用内毒素刺激。最后，将正常单核细胞与含有抗IL-10抗体或抗TGF-β抗体的脓毒症血清一起孵育，然后用内毒素刺激。测量：通过酶联免疫吸附测定法测量血清和培养上清液中的TNF-α、IL-10和TGF-β水平。脓毒症血清中IL-10和TNF-α水平显著升高，而TGF-β水平与对照组无差异。正常单核细胞增加TNF-α和IL-10的释放响应于内毒素。相比之下，脓毒症单核细胞TNF-α释放响应于内毒素而减弱（1.8 +/- 0.5 vs. 1.0 +/- 0.4 ng/mL，刺激vs.基线），而IL-10释放从基线显著增加（173 +/- 91 vs. 8 +/- 4 pg/mL，刺激vs.基线）。正常单核细胞与脓毒血清的孵育减弱了响应于内毒素的TNF-α释放（正常血清的32% +/-8%; p <0.01），而IL-10释放增加（正常血清的285% +/-84%; p <0.05）。当将正常单核细胞与脓毒症血清和抗IL-10抗体一起孵育时，TNF-α释放显著增加至正常血清的75% +/-17%（p <0.05，与脓毒症血清相比）。孵育正常的单核细胞与抗TGF-抗体没有显着影响TNF-α或IL-10的释放在响应tetoxic.Conclusion：从感染性休克患者的单核细胞表现出持续的IL-10释放的时间时，TNF-α释放下调。IL-10的持续释放可能导致单核细胞促炎细胞因子释放受损和感染性休克中免疫功能障碍的发展。
Objectives: The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-beta in monocyte hyporesponsiveness during septic shock.Design: Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed. Next, normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin. Finally, normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-beta antibodies and then stimulated with endotoxin.Measurements: TNF-alpha, IL-10, and TGF-beta levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay.Setting: Research laboratory.Main Results: IL-10 and TNF-alpha levels were significantly increased in septic serum, whereas TGF-beta levels were not different from controls. Normal monocytes increased TNF-alpha and IL-10 release in response to endotoxin. In contrast, septic monocyte TNF-alpha release was attenuated in response to endotoxin (1.8 +/- 0.5 vs. 1.0 +/- 0.4 ng/mL, stimulated vs. baseline), whereas IL-10 release increased significantly from baseline (173 +/- 91 vs. 8 +/- 4 pg/mL, stimulated vs, baseline). Incubation of normal monocytes with septic serum attenuated TNF-alpha release in response to endotoxin (32% +/- 8% of normal serum; p < .01), whereas IL-10 release was increased (285% +/- 84% of normal serum; p < .05). When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies, TNF-alpha release increased significantly to 75% +/- 17% of normal serum (p < .05 vs. septic serum atone). Incubation of normal monocytes with anti-TGF- antibodies did not significantly affect either TNF-alpha or IL-10 release in response to endotoxin.Conclusion: Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-alpha release is downregulated. The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock.